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Mol Ther. 2018 Apr 4;26(4):1008-1019. doi: 10.1016/j.ymthe.2018.01.019. Epub 2018 Jan 31.

Pre-existing Immunity to Oncolytic Virus Potentiates Its Immunotherapeutic Efficacy.

Author information

1
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Swim Across America-Ludwig Collaborative Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
2
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
3
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Swim Across America-Ludwig Collaborative Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
4
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Swim Across America-Ludwig Collaborative Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Weill Cornell Medical College, New York, NY 10065, USA.
5
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Swim Across America-Ludwig Collaborative Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Weill Cornell Medical College, New York, NY 10065, USA. Electronic address: zamarind@mskcc.org.

Abstract

Anti-viral immunity presents a major hurdle for systemically administered oncolytic viruses (OV). Intratumoral OV therapy has a potential to overcome this problem through activation of anti-tumor immune response, with local and abscopal effects. However, the effects of anti-viral immunity in such a setting are still not well defined. Using Newcastle Disease Virus (NDV) as a model, we explore the effects of pre-existing anti-viral immunity on therapeutic efficacy in syngeneic mouse tumor models. Unexpectedly, we find that while pre-existing immunity to NDV limits its replication in tumors, tumor clearance, abscopal anti-tumor immune effects, and survival are not compromised and, on the contrary, are superior in NDV-immunized mice. These findings demonstrate that pre-existing immunity to NDV may increase its therapeutic efficacy through potentiation of systemic anti-tumor immunity, which provides clinical rationale for repeated therapeutic dosing and prompts investigation of such effects with other OVs.

KEYWORDS:

NDV; Newcastle Disease Virus; cancer immunotherapy; immuno-oncology; oncolytic virus; pre-existing immunity; tumor immunology

PMID:
29478729
PMCID:
PMC6079372
DOI:
10.1016/j.ymthe.2018.01.019
[Indexed for MEDLINE]
Free PMC Article

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